Exosome-anchored scholzite conversion coating on titanium with long-term stability and immunomodulatory ability to enhance osteogenesis

• Published in: Chemical engineering journal (Lausanne, Switzerland : 1996) Switzerland : 1996), 2025-01, Vol.503, p.158142, Article 158142
• Main Authors: Dai, Shimin, Huang, Benzhao, Wang, Peng, Lu, Xiaoqing, Li, Shishuo, Zhao, Zhibo, Li, Xiao, Li, Ningbo, Yu, Jiahui, Man, Zhentao, Li, Wei, Liu, Bing
• Format: Article
• Language: English
• Subjects: Exosome; Immunomodulation; Osteogenesis; Scholzite coating; Titanium
• ISSN: 1385-8947
• DOI: 10.1016/j.cej.2024.158142

[Display omitted] •A scholzite coating is produced on Ti by phosphate chemical conversion.•Scholzite-coated Ti can stably sequester exosomes via DSPE-PEG linking.•The anchored exosomes present a unique ‘on demand’ release pattern.•Scholzite coating coupled with exosomes promote M2 polarization of macrophages.•The exosomes-loaded Ti with immunomodulatory property enhance osteogenesis. Exosomes (exos) as potent acellular therapeutic agents have been widely investigated to modify the surfaces of biomaterials to promote bone formation in recent decade. However, effective immobilization of exos is challenging on the surface of metal-based implants. In this study, we developed a simple yet versatile approach for the immobilization of bone marrow stem cell (BMSC)-derived exos onto titanium (Ti) implants, featuring high exos loading capacity and prolonged retention. First, a micro-/nano-structured scholzite (CaZn2(PO4)2·2H2O) coating was fabricated on Ti using a phosphate chemical conversion method. Next, an FDA-approved phospholipid–polymer conjugate, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol (DSPE-PEG), was used to link the exos and coated Ti together by in situ anchoring. The anchored exos on the coated Ti presented a unique “on-demand” delivery pattern and could be phagocytosed by adherent cells, effectively enhancing BMSC adhesion, spreading, and osteogenic differentiation on Ti. Additionally, the scholzite coating in cooperation with exos exerted a robust immunomodulatory effect by suppressing M1 macrophages while promoting M2 macrophages. The resulting favorable osteoimmune microenvironment accelerated osteogenesis both in vitro and in vivo, possibly via the crosstalk of integrin/FAK signaling pathways. This study suggests a novel route for integrating bioactive exos with clinical metal implants and demonstrates a promising perspective for designing biomaterials with osteoimmunomodulatory functions.